Publications
Here is a selection of publications where different laminin isoforms were used to create more authentic cell culture systems.
Enhanced xeno-free differentiation of hiPSC-derived astroglia applied in a blood–brain barrier model
Louise Delsing, Therése Kallur, Henrik Zetterberg, Ryan Hicks, Jane Synnergren. Fluids Barriers CNS, 2019
This study shows that astroglia cells differentiated on Biolaminin 521 display an improved phenotype compared to a mouse EHS-extracted laminin L2020 product. Especially, cells differentiated on Biolaminin 521 had a higher secretion of factors important for BBB formation, such as GFAP, S100B, and Angiopoietin-1, than cells differentiated on the laminin extract. In addition, glutamate uptake and the ability to induce the expression of junction proteins in endothelial cells were affected by the culture matrix choice. The study showed differentiation of functional astroglia from three different human induced pluripotent stem cell lines which were used in a blood-brain barrier model.
Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model
Zengping Liu, Tanja Ilmarinen, Gavin S. W. Tan, Heidi Hongisto, Edmund Y. M. Wong, Andrew S. H. Tsai, Sami Al-Nawaiseh, Graham E. Holder, Xinyi Su, Veluchamy Amutha Barathi, Heli Skottman & Boris V. Stanzel Stem Cell Research & Therapy, 2021
This surgical xenotransplantation study addressed logistical, surgical, and immunosuppression-related issues in cell therapy. Biolaminin 521 -coated transplant sheets with live stem-cell-derived retinal pigment epithelium (RPE) cells were transported from the manufacturing site (Finland) to the transplantation site (Singapore), taking more than 30 hours, without any alterations in cell quality. Laminin-521 was also part of the clinically compliant differentiation protocol from embryonic stem cells to RPE cells. The process overall resulted in functional submacular xenograft integrations.
Culture surface protein coatings affect the barrier properties and calcium signalling of hESC-RPE
Taina Viheriälä, Juhana Sorvari, Teemu O. Ihalainen, Anni Mörö, Pyry Grönroos, Sabrina Schlie-Wolter, Boris Chichkov, Heli Skottman, Soile Nymark & Tanja Ilmarinen Scientific Reports, 2021
Biolaminin 521 was shown to significantly improve hESC-derived retinal pigment epithelial cell attachment and the formation of an intact epithelium after cryopreservation. Laminin-521 significantly improved cell attachment and epithelium barrier properties when compared to collagen (Col-IV) alone. The cryopreserved cells attached poorly to collagen only. Laminin was thus able to provide the needed support for differentiated therapeutic cells which usually require cryostorage before transplantation.
Generation of 3D retinal tissue from human pluripotent stem cells using a directed small molecule-based serum-free microwell platform
Hassan Rashidi, Yeh Chwan Leong, Kerrie Venner, Hema Pramod, Qi-Zhen Fei, Owen J. R. Jones, Dale Moulding & Jane C. Sowden Scientific Reports, 2022
Biolaminin 521 (LN521) was used as the matrix in a 2D/3D system for retinal differentiation from human pluripotent stem cells in an agarose micromould platform. To achieve a serum-free and animal-free protocol for producing retinal tissue with photoreceptor cells, the scientists successfully replaced Matrigel (which is derived from mouse tumor cells) with laminin-521, and fetal bovine serum (FBS) with human platelet lysate (HPL). The culture system first allows cells to self-organize forming neuroepithelial structures that resemble embryonic optic vesicles, and then mimics retinogenesis and produces retinal tissue with photoreceptor cells. The generated photoreceptors exhibited key photoreceptor cell features including the formation of OS-like structures containing proteins involved in phototransduction.
An SCPPPQ1/LAM332 protein complex enhances the adhesion and migration of oral epithelial cells: Implications for dentogingival regeneration
Shahrzad Nouri, James Holcroft, Laura-lee Caruso, Thu V. Vuong, Craig A. Simmons, Emma R. Master, Bernhard Ganss. Acta Biomaterialia, 2022
This study showed the first evidence of the functional role of laminin 332 (Biolaminin 332) and an enamel protein SCPPQ1 in the epithelial attachment of the gum, the junctional epithelium (JE), to the tooth hydroxyapatite surfaces. The strongly interacting proteins favored oral epithelial cell attachment and high migration rate. The LN332-SCPPQ1 (LAM332-SCPPQ1) complex has the potential to be further developed as a bioadhesive material to enhance JE structural integrity and attachment - a feature that often fails in common periodontal disease treatments.
p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521
Mingyang Ma, Shuyao Hua, Xiangde Min, Liang Wang, Jun Li, Ping Wu, Huifang Liang, Bixiang Zhang, Xiaoping Chen,and Shuai Xiang. Signal Transduct Target Ther. 2022
This study identified Biolaminin 521 as an ideal substrate for rat hepatic progenitor cell (HPC) culture. In liver tissue, HPC populations are located in a laminin-rich environment, and laminin is known to be required for HPC proliferation. This study showed that especially laminin-521 isoform improved proliferation rate in comparison to EHS extract (Matrigel), fibronectin, an undefined laminin extract, and other Biolaminin isoforms. The increase in proliferation was shown to be linked with increased p53 protein stability.
Toward Xeno-Free Differentiation of Human Induced Pluripotent Stem Cell-Derived Small Intestinal Epithelial Cells
Jaakko Saari, Fatima Siddique, Sanna Korpela, Elina Mäntylä, Teemu O. Ihalainen, Katri Kaukinen, Katriina Aalto-Setälä, Katri Lindfors, and Kati Juuti-Uusitalo. International Journal of Molecular Sciences, 2022
Small intestinal epithelial cells were differentiated from induced pluripotent stem cells (iPSC-SIEC), via definitive endoderm, on Biolaminin 511. The aim of the study was to develop a protocol with animal-free components to reduce variation in experimental outcomes. The differentiated cells cultured on laminin exhibited more enterocyte specific cellular functionality than cells on Geltrex or collagen. The protocol is serum-free and can be easily modified as completely xeno-free by culturing iPSCs on Biolaminin 521 matrix and changing the B27 and N2 supplement to available xeno-free versions.
A Biomimetic Electrospun Membrane Supports the Differentiation and Maturation of Kidney Epithelium from Human Stem Cells
Mou, X., Shah, J., Bhattacharya, R., Kalejaiye, T.D., Sun, B., Hsu, P.-C., Musah, S Bioengineering, 2022
Laminin (Biolaminin 511) was shown to be crucial for the differentiation of hPSCs into mature kidney glomerular podocytes on electrospun silk fibroin. Without laminin functionalization, the cells were poorly attached and scarce having small and rounded morphology. Electrospun silk fibroin membranes are biomimetic scaffolds, mimicking the surface topography of the glomerulus. These kinds of biomaterials can be integrated into microphysiological systems, such as microfluidic organ-on-chip devices or co-culture systems for modelling tissue development and disease.
Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models
Anders Lundin, Louise Delsing, Maryam Clausen, Piero Ricchiuto, José Sanchez, Alan Sabirsh, Mei Ding, Jane Synnergren, Henrik Zetterberg, Gabriella Brolén, Ryan Hicks, Anna Herland, and Anna Falk Stem Cell Reports, 2018
This study reports the differentiation of human induced pluripotent stem cell (hiPSC)-derived astroglia cells under defined conditions using Biolaminin 521 as the matrix.
Pluripotent stem cell-derived cardiovascular progenitors differentiated on laminin 221 regenerate and improve function of infarcted swine hearts
Yap L, Chong LY, Tan C, Adusumalli S, Seow M, Guo J, Cai Z, Loo SJ, Lim E, Lath N, Ye L, Petretto E, Tryggvason K. BiorXiv, 2021
The authors report a highly reproducible, chemically defined and fully humanized differentiation method of hESCs for the generation of potent cardiovascular progenitors (CVPs), using laminin-221 (Biolaminin 221) as the culture matrix. Transplantation of the CVPs into the myocardial infarcted pig hearts yielded maturation of the progenitor cells to cardiomyocytes and improved cardiac function using only 200 million CVPs, without fatal ventricular arrhythmia occurring. The results may have a significant impact on regenerative cardiology and the method is intended to be used in stem cell therapy of myocardial infarction in humans.